中美仿制药研发和申报流程概述.pptxVIP

中美仿制药研发和申报流程涂家生， Ph. D.中国药科大学药剂学教授Tel: 025mail: jiashengtu@yahoo 2021.11 郑州 我国仿制药申报、审评和研发对策主要内容中美关于原研药和仿制药的背景美国仿制药：申报、基于问题的审评和研发对策展望1234 药物经济学催生美国仿制药制度美国社会平安制度导致政府赤字严重SSA已经破产：如何破局？降低医疗费用成为必然Hatch-Waxman法案出台美国FDA药品注册申请：新药〔两类〕、仿制药和非处方药申请 1984年后New Drug Applications(NDAs)Abbreviated New Drug Applications (ANDAs) “Full Reports〞 of Safety and Efficacy Investigations Applicant has right of reference to essential investigations? Duplicate of an already approved product No safety/efficacy data permitted (only bioequivalence) YESNO505(b)(1)505(b)(2)505(j) NDA的研发和申报 505(b)(1) 新药申报资料内容IndexSummaryChemistry, Manufacturing and ControlSamples, Methods Validation Package and LabelingNonclinical Pharmacology and Toxicology 6. Human Pharmacokinetics and Bioavailability7. Microbiology ( for anti-microbial drugs only)8. Clinical Data9. Safety Update report ( typically submitted 120 days after the NDA’s submission ) 10. Statistical11. Case Report Tabulations12. Case Report Forms13. Patent Information14. Patent Certification 505(b)(2): 历史过程Hatch Waxman法案：1984Parkman LetterPhantom ANDAFDA Draft Guidance for Industry (1999)FDA Response to Citizen’s Petition (2003)可以降低研发的费用和审评力量的浪费 505(b)(2)的关键: 可靠性What is “Reliance〞By whom?On what?Reliance and ExclusivityMarket vs. Data ExclusivitySafety/Efficacy Data vs. CMC dataFDA Process for Determining RelianceWho, when and how? 505(b)(2)的意义介于全创新药物和仿制药之间具有专利保护，且不存在产权纠纷和仿制药不同，无替换的要求 应有突破 505(b)(2)范围New Chemical Entity (rarely)：我国New dosage form：我国5类New dosing regimen：我国补充申请New strength：我国补充申请New route of administration：我国2类New indication：我国1.6 505(b)(2)情形New active ingredient (different salt, ester, complex, chelate, clathrate, racemate, or enantiomer of active moiety)New inactive ingredient that requires more than limited confirmatory studiesRx ? OTC switchNew Combination Products“Generic biologics〞 505(b)(2)排他性Exclusivities available for 505(b)(2) productsNCE Exclusivity (5 years)New Product Exclusivity (3 years)Orphan Drug Exclus